1. Field Of The Invention
This invention relates to antibody hybride. More particularly, it relates to antibody hybrids in which an organic moiety is covalently bonded to the antibody at a preselected location on the antibody so as to preserve the normal functionality of the antibody.
Antibody molecules exist in one of several classes. To date, five known classes (isotypes) in the higher vertebrates are designated as immunoglobulin (Ig) IgM, IgA, IgG, IgD, or IgE. The common structure for these immunoglobulins is a monomer composed of two heavy chains and two light chains. Heavy and light chains are covalently linked to each other by disulfide bonds and the two heavy chains are linked through disulfide bonds. Two of the immunoglobulin classes, IgM and IgA, exist naturally in a polymeric form. Polymers of the four chain structures are linked via the cysteine residue located in proximity to the carboxyl terminus on the constant region of the heavy chains.
The first step of polymerization of IgM or IgA is dimer formation. In the usual naturally occurring situation the penultimate carboxyl cysteine residue of two monomers are joined via a 20,000 dalton polypeptide joining or `J` chain. After dimerization, pentamer formation of IgM is completed enzymatically by a thiol oxidoreductase. Richard A. Roth and Marion E. Koshland, "Identification of a Lymphocyte Enzyme That Catalyzes Pentamer Immunoglobulin M Assembly," Journal of Biological Chemistry, (1981) 256(9):4633-9. Polymerization of IgA is also initiated by J chain assembly. IgA molecules exist predominately as dimers and are not believed to utilize any other enzyme systems for further polymerization. Thus, homopolymers of monomer IgM or IgA are assembled in vivo via the cysteine residue near the carboxyl terminal end. The disulfide bonds at this position covalently link the monomers.
This invention presents a methodology for chemically linking carboxyl-terminal sulfhydryl residues of monoclonal antibodies to form hybrid molecules. These hybrid molecules are defined in the preferred embodiment as an antibody of the IgM or IgA class linked to another component including an antibody, enzyme, hormone, toxin or carrier protein (a protein which acts only as a delivery and amplification system for smaller molecular weight components) in which the carrier protein may contain a suitable labeling agent or a suitable cytotoxic agent.
2. Description Of The Prior Art